First Line Treatment in EGFR Mutation Positive Advanced NSCLC Patients With Central Nervous System (CNS) Metastases
BM
A Randomized, Open-label, Controlled, Multi-Center Phase II/III Study to Assess the Efficacy and Safety of AZD3759 vs. a Standard of Care EGFR TKI, as First Line Treatment to EGFR Mutation Positive Advanced NSCLC With CNS Metastases
1 other identifier
interventional
492
4 countries
58
Brief Summary
The first-line treatment with single agent AZD3759 results in superior Progression Free Survival (PFS) compared to Standard of Care (SoC) Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKI), in patients with advanced EGFR mutation positive non-small cell lung cancer (NSCLC) with Central Nervous System (CNS) metastasis
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 nonsmall-cell-lung-cancer
Started Oct 2018
Typical duration for phase_2 nonsmall-cell-lung-cancer
58 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 22, 2018
CompletedFirst Posted
Study publicly available on registry
August 31, 2018
CompletedStudy Start
First participant enrolled
October 29, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 12, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 12, 2022
CompletedSeptember 10, 2025
September 1, 2025
3.7 years
August 22, 2018
September 3, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
PFS assessed by Blinded Independent Central Radiological
To assess if first line treatment with AZD3759 results in significant PFS efficacy compared to Gefitinib or Erlotinib as determined by Blinded Independent Central Radiological (BICR) review using RECIST 1.1.
48 months
Secondary Outcomes (29)
PFS assess by investigator
48 months
Intracranial PFS (iPFS) assessed by investigator
48 months
Intracranial PFS (iPFS) assessed by BICR
48 months
Extracranial PFS (ePFS) assessed by investigator
48 months
Extracranial PFS (ePFS) assessed by BICR
48 months
- +24 more secondary outcomes
Other Outcomes (2)
Pop-PK analysis
48 months
Exposure-Response analysis
48 months
Study Arms (2)
AZD3759 Group
EXPERIMENTALAZD3759 group will receive a 200 mg twice daily dose of AZD3759
Erlotinib or Gefitinib Group
ACTIVE COMPARATORSoC EGFR-TKI Erlotinib or Gefitinib Group will get EGFRTKI Erlotinib 150 mg or Gefitinib 250 mg PO Q.D
Interventions
Eligibility Criteria
You may qualify if:
- Properly completed patient informed consent
- Male or female aged at least 18 years
- Histologically or cytologically confirmed diagnosis of NSCLC with activating EGFR mutations including L858R and/or Exon19Del. EGFR mutation status will be determined by local or central laboratory testing on tumour tissue or plasma utilizing a validated methodology which has been approved by the regulatory authority.
- No prior treatment with chemotherapy, EGFR-TKIs, or biological therapies that are considered first line treatment for advanced NSCLC.
- All patients must have a documented diagnosis of advanced (Stage IV) NSCLC with Magnetic Resonance Imaging (MRI) documented CNS metastases that include brain metastases (BM). BM + patients with co- existent leptomeningeal involvement are eligible for the study.
- Eligible patients are not candidates for definitive surgical resection or radiation of all lesions in the opinion of the treating physician.
- All patients must be stable without any systemic (oral or parenteral) corticosteroid or anticonvulsant therapy for at least 2 weeks prior to study treatment. Inhaled non-absorbable and topical corticosteroid use are permitted as indicated.
- Patients may have prior placement of a properly functioning CNS shunt or Ommaya reservoir.
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks.
- Women of child-bearing potential and male subjects shall agree to take medically acceptable contraception measures while on study treatment and for 3 months following completion of study treatment. All women of child-bearing potential must have a negative blood pregnancy test at screening.
- (a) For Patients with measurable CNS lesions must have AT LEAST ONE site of CNS lesion, which was not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter by MRI and which is suitable for accurate repeated measurements. Measurable extracranial disease is not required. (b) For Patients with non-measurable CNS lesions must have AT LEAST ONE extracranial lesion, which has not been previously irradiated, within the screening period that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) by CT/MRI and are suitable for accurate repeated measurement.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (58)
China site
Hefei, Anhui, 230001, China
China site
Chongqing, China, 400037, China
China site
Fuzhou, Fujian, 350014, China
China site
Xiamen, Fujian, 361003, China
China site
Guangzhou, Guangdong, 510080, China
China site
Guangzhou, Guangdong, 510180, China
China site
Haerbin, Heilongjiang, 150081, China
China site
Zhengzhou, Henan, 450008, China
China site
Zhengzhou, Henan, 450052, China
China site
Wuhan, Hubei, 430022, China
China site
Wuhan, Hubei, 430030, China
China site
Wuhan, Hubei, 430079, China
China site
Yichang, Hubei, 443003, China
China site
Changsha, Hunan, 410013, China
China site
Nanjing, Jiangsu, 210002, China
China site
Nanjing, Jiangsu, 210009, China
China site
Suzhou, Jiangsu, 215004, China
China site
Wuxi, Jiangsu, 214062, China
China site
Xuzhou, Jiangsu, 221002, China
China site
Yangzhou, Jiangsu, 225001, China
China site
Changchun, Jilin, 130012, China
China site
Changchun, Jilin, 130021, China
China site
Xi'an, Shaanxi, 710061, China
China site 0123
Jinan, Shandong, 250117, China
China site
Linyi, Shandong, 276000, China
China site
Weifang, Shandong, 261000, China
China site
Yantai, Shandong, 264000, China
China site
Chengdu, Sichuan, 610041, China
China site
Kunming, Yunnan, 650118, China
China site
Hangzhou, Zhejiang, 310003, China
China site
Hangzhou, Zhejiang, 310022, China
China site
Hangzhou, Zhejiang, 311100, China
China site
Beijing, 100021, China
China site
Beijing, 100071, China
China site
Beijing, 100142, China
China site
Beijing, 100730, China
China site
Chongqing, 400030, China
China site
Chongqing, 400042, China
China site
Shanghai, 200030, China
China site
Shanghai, 200032, China
China site
Tianjin, 300052, China
Singapore site
Singapore, 308433, Singapore
Korea site
Daegu, 42415, South Korea
Korea site
Gyeonggi-do, 16247, South Korea
Korea site
Gyeongsang, 52727, South Korea
Korea site
Incheon, 21565, South Korea
Korea Site
Jungbuk, 28644, South Korea
Korea Site
Seoul, 03080, South Korea
Korea site
Seoul, 05368, South Korea
Korea Site
Seoul, 06351, South Korea
Korea site
Seoul, 06591, South Korea
Korea site
Seoul, 07061, South Korea
Korea site
Suwon, 16499, South Korea
Korea site
Ulsan, 44033, South Korea
Taiwan site
Taichung, 407, Taiwan
Taiwan site
Tainan, 704, Taiwan
Taiwan site
Taipei, 100, Taiwan
Taiwan site
Taoyuan District, 333, Taiwan
Related Publications (1)
Zhou Q, Yu Y, Xing L, Cheng Y, Wang Y, Pan Y, Fan Y, Shi J, Zhang G, Cui J, Zhou J, Song Y, Zhuang W, Ma Z, Hu Y, Li G, Dong X, Feng J, Lu S, Wu J, Li J, Zhang L, Wang D, Xu X, Yang TY, Yang N, Guo Y, Zhao J, Yao Y, Zhong D, Xia B, Yang CT, Zhu B, Sun P, Shim BY, Chen Y, Wang Z, Ahn MJ, Wang J, Wu YL. First-line zorifertinib for EGFR-mutant non-small cell lung cancer with central nervous system metastases: The phase 3 EVEREST trial. Med. 2025 Jan 10;6(1):100513. doi: 10.1016/j.medj.2024.09.002. Epub 2024 Oct 9.
PMID: 39389055BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Yilong Wu, M.D.
Guangdong Provincial People's Hospital
- PRINCIPAL INVESTIGATOR
Myung-Ju Ahn, M.D.
Samsung Medical Center, Sungkyunkwan University School of Medicine
- PRINCIPAL INVESTIGATOR
Jie Wang, M.D.
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
- PRINCIPAL INVESTIGATOR
Qing Zhou, M.D.
Guangdong Provincial People's Hospital
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 22, 2018
First Posted
August 31, 2018
Study Start
October 29, 2018
Primary Completion
July 12, 2022
Study Completion
July 12, 2022
Last Updated
September 10, 2025
Record last verified: 2025-09
Data Sharing
- IPD Sharing
- Will not share